Design, synthesis, and biological evaluation of novel asiatic acid derivatives as potential anticancer agents

作者：Goncalves Bruno M F; Salvador Jorge A R^*; Santos Diana S M; Marin Silvia; Cascante Marta^*

来源：RSC Advances, 2016, 6(45): 39296-39309.

DOI：10.1039/c6ra04597a

A series of new asiatic acid derivatives modified in the A-ring and at C-28 were synthesized and their antiproliferative activity was evaluated against HT-29 and HeLa cell lines. Most of the derivatives tested here exhibited improved antiproliferative activity compared with asiatic acid. Among them, the best compounds, 7 and 8, were further evaluated against additional cancer cell lines (MCF-7, Jurkat, and PC-3 cells) and a nontumoral cell line (BJ). The most active compound, 7, exhibited IC50 values ranging from 1.62 mu M in HeLa cells to 9.93 mu M in MCF-7 cells. Further studies revealed that compound 7 arrested the cell cycle at the G0/G1 phase and induced caspase-dependent apoptosis in HeLa cells. Furthermore, this compound showed selectivity toward cancer cells, and a synergistic effect was observed after simultaneous treatment of HeLa cells with compound 7 and cisplatin. Collectively, our results suggest that compound 7 may be useful for the development of new anticancer therapies; thus, additional preclinical studies are warranted.

• 出版日期2016